Drug discovery campaigns are often remembered for the final molecule that reaches the clinic. Less visible—but equally important—is the assay strategy that made the discovery possible. The identification of GDC-8264 by researchers at Genentech revealed a potent and selective RIP1 kinase inhibitor now in Phase 2 clinical development. This provides a clear example of how […]
Phosphodiesterase 5 (PDE5) is most familiar in connection to sildenafil (Viagra), a popular pharmaceutical PDE5 inhibitor. In response to nitric acid-activated soluble guanylyl cyclase production of cGMP, dimeric PDE5 binds and hydrolyzes cGMP in vascular smooth muscles cells, lung, kidney, brain, cardiac myocytes, and platelets to create 5′-GMP. This is accomplished by cGMP binding to […]
The PIK3CA gene codes for the 110 kDa catalytic subunit (p110α) of phosphoinositide 3-kinase (PI3Ka). Together with its regulatory component, p85α (encoded by PIK3R), they comprise the powerful PI3Ka heterodimer. This heterodimer conducts growth impulses from multiple cell surface receptor tyrosine kinases (RTKs) to the interior of the cell. It is known that individual missense […]
Researchers at the University of Tubingen use Transcreener to uncover how residence time works on a molecular level with p38α MAPK Inhibitors – Many factors affect the effectiveness of ligand-substrate or drug-target interactions. Conformational docking and stearic considerations help inform optimal “fits.” Ligand moiety solubility, both in free and bound forms, is also a consideration […]
Genentech discovers IRAK4 inhibitors using the Transcreener Kinase Assay Kit – IRAK is also known as Interluekin-1 Receptor Associated Kinase. There are four different proteins within this group, including IRAK1, IRAK2, IRAK3, and IRAK4. Each of these mediates interaction with MyD88 and its associated adaptor proteins. IRAK1 and IRAK4 are active enzymes that exhibit kinase […]
Newly expressed human Hsp70 activity now being studied – Heat shock protein 70 (Hsp70) is known for its upregulation during times of stress in order to maintain homeostasis. Like other heat shock proteins, Hsp70 is a chaperone protein that assists other proteins in correctly folding to become fully active molecules. It binds to damaged, misfolded, […]
Researchers look to discover a CPS1 inhibitor with an eye on cancer – Without properly functioning carbamoyl-phosphate synthetase I (CPS1), large amounts of highly toxic ammonia is able to accumulate in the body contributing to neurological conditions.2 Increased levels of the enzyme have been found in some cancers including lung adenocarcinoma (LADC).1 When overexpressed, CPS1 […]
PI3K Inhibitors and Cancer – Although cancer is widespread, determining the culprit, as well as individual treatment, is challenging. A variety of cancer types exist with a multitude of contributors. Being the most common human genetic disease, a whole host of genes are involved. Some contribute to curbing cancer (tumor suppressor genes), while oncogenes promote […]
Genentech discovers novel RIPK1 inhibitors – Like other serine/threonine protein kinases, receptor-interacting serine/threonine-protein kinase 1 (RIPK1) plays a role in several signaling pathways that keep us living healthy, functioning lives. RIPK1 is one of those enzymes’ that wears a variety of hats depending on what function needs attention. It contributes to cell death as well […]
Measuring Rab interaction with a GTPase Assay – GTPases are in the limelight in biology and drug discovery because of their role in a wide range of cellular processes and functions. They are highly conserved regulatory proteins involved in such diverse roles as signal transduction, protein biosynthesis, cell adhesion, membrane remodeling and trafficking, cytoskeletal reorganization, […]
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